Film coating for tablets and caplets

ABSTRACT

The present invention relates to novel coating compositions for application to solid dosage forms such as tablets or caplets, solid dosage forms coated with the composition, and methods of preparing said coating compositions.

The present invention relates to novel coating compositions forapplication to solid dosage forms such as tablets or caplets, soliddosage forms coated with the composition, and methods of preparing saidcoating compositions.

EP-A-0 891 180 describes a process for encapsulation of caplets in acapsule wherein caplets are encapsulated in capsule shells. To obtaintamper-proof solid dosage forms, the caplets which are to be includedinto capsule shells, are coated with an acceptable coating for capletprocessing. As described in EP-A-0 891 180 said coating is selected froma material selected from the group consisting of cellacephate, polyvinylacetate phthalate, methacrylic acid polymers, hypromellose phthalate,hydroxyalkyl methyl cellulose phthalates or mixtures thereof.

After being coated with such a coating the caplet is usually feeded on avibratory feed, filled into capsule shell parts and the encapsulateddosage form is dried so as to obtain capsules.

In several studies carried out by the present invention on finishedcapsules prepared as mentioned above, it has, however, been found thatafter obtaining said capsules the shell parts can be removed so as tolay free intact shell parts and caplets.

This should be prohibited so as to avoid any exchange of the capletscontained in said capsules by non-authorized persons after putting saidcapsules on the market.

Object of the present invention therefore is to provide coatingcompositions which give raise to capsules in a tamper-proof form whichcannot be easily freed from the shell parts without deteriorating theshell parts and/or the caplets.

It is another object of the present invention to provide a coatingcomposition which improves a feeding of solid dosage forms such ascaplets or tablets, coated with said coating composition, on a vibratoryfeed used for example in a capsule manufacturing process.

It is yet another object of the present invention to provide a methodfor coating solid dosage form such as caplets or tablets with saidcoating composition.

It is yet another object of the present invention to provide a methodfor encapsulating caplets in a capsule in a tamper-proof form.

According to a first aspect, the present invention provides a coatingcomposition comprising a film forming agent in an amount of from 0 toabout 85% by weight, an adhesion enhancing agent in an amount of fromabout 10 to about 90% by weight, and a glidant in an amount of fromabout 5 to about 50% by weight, based on the weight of the coatingcomposition.

According to a second aspect the present invention provides a soliddosage form coated with a coating composition comprising a film formingagent in an amount of from 0 to about 85% by weight, an adhesionenhancing agent in an amount of tram about 10 to about 90% by weight,and a glidant in an amount of from about 5 to about 50% by weight, basedon the weight of the coating composition.

According to a third aspect, the present invention provides a method ofpreparing a coating composition comprising bringing into association afilm forming agent in an amount of from 0 to about 85% by weight, anadhesion enhancing agent in an amount of from about 10 to about 90% byweight, and a glidant in an amount of from about 5 to about 50% byweight, based on the weight of the coating composition.

According to a forth aspect, the present invention provides a method ofpreparing a solid dosage form which comprises coating a solid dosageform core with a coating composition comprising a film forming agent inan amount of from 0 to about 85% by weight, an adhesion enhancing agentin an amount of from about 10 to about 90% by weight, and a glidant inan amount of from about 5 to about 50% by weight, based on the weight ofthe coating composition.

In a preferred embodiment of the first aspect said coating compositioncomprises a film forming agent in an amount of from about 0 to about 40%by weight, an adhesion enhancing agent in an amount of from about 35 toabout 80% by weight, and a glidant in an amount of from about 5 to about25% by weight, based on the weight of the coating composition.

In an especially preferred embodiment of the first aspect said coatingcomposition comprises a film forming agent in an amount of about 20% byweight, an adhesion enhancing agent in an amount of about 60% by weight,and a glidant in an amount of about 20% by weight, based on the weightof the coating composition.

In another especially preferred embodiment of the first aspect saidcoating composition comprises a film forming agent in an amount of about30% by weight, an adhesion enhancing agent in an amount of about 50% byweight, and a glidant in an amount of about 20% by weight, based on theweight of the coating composition.

In another especially preferred embodiment of the first aspect saidcoating composition comprises an adhesion enhancing agent in an amountof about 80% by weight, and a glidant in an amount of about 20% byweight, based on the weight of the coating composition.

Examples of said film forming agent suitable for incorporation into thecoating composition of the first aspect of the present invention includecellulosephthalateacetate, microcrystalline cellulose, methylcellulose,hydroxypropyl methylcellulose, alginates, gum arabic,carboxymethylcellulose, hydroxyethylcellulose and methylcellulose.

Preferred film forming agents to be used according to the first aspectof the present invention are methylcellulose, hydroxypropylmethylcellulose, gum arabic, carboxymethylcellulose,hydroxyethylcellulose and methylcellulose, more preferable hydroxypropylmethylcellulose.

Examples of said adhesion enhancing agent suitable for incorporationinto the coating composition of the first aspect of the presentinvention include dextrose, sorbitol, mannitol, sucrose,polyvinylpyrrolidone, lactose, starch, sodium starch glycolate,hydroxypropylcellulose, ethylcellulose and maltodextrines.

Preferred adhesion enhancing agents suitable for incorporation into thecoating composition of the first aspect of the present invention aresucrose, polyvinylpyrrolidone, hydroxypropylcellulose, ethylcelluloseand maltodextrines, more preferable hydroxypropylcellulose.

Examples of said glidant suitable for incorporation into the coatingcomposition of the first aspect of the present invention includepolyethylene glycol, polypropylene glycol, triethyl citrate, mono-, di-or triacetates of glycerol and 1,2-propyleneglycol.

A preferred glidant suitable for incorporation into the coatingcomposition of the first aspect of the present invention is polyethyleneglycol.

Usually, the coating composition according to the first aspect has a gelpoint of about 40° C. or more, i.e. close to the transition point.

The solid dosage form coated with a coating composition, of the secondaspect of the present invention usually is a caplet or a tablet to becoated with the coating composition of the present invention.

According to a further aspect of the present invention, there isprovided a method of preparing a coating composition comprising bringinginto association a film forming agent in an amount of from 0 to about85% by weight, an adhesion enhancing agent in an amount of from about 10to about 90% by weight, and a glidant in an amount of from about 5 toabout 50% by weight, based on the weight of the coating composition.

According to a further aspect of the present invention, there isprovided a method of preparing solid dosage form which comprises coatinga solid dosage form core with a coating composition comprising a filmforming agent in an amount of from 0 to about 85% by weight, an adhesionenhancing agent in an amount of from about 10 to about 90% by weight anda glidant in an amount of from about 5 to about 50% by weight, based onthe weight of the coating composition.

Usually, said solid dosage form is a caplet or a tablet, preferably acaplet.

In one embodiment of the forth aspect of the present inventionthereafter one or more caplets coated with said coating composition, canbe filled into at least one capsule part so as to obtain capsules.

The capsule shell in which the caplet is to be enclosed preferablycomprises two shell halves, a body portion and a cap portion. Othercapsule shells comprising more than two parts are also possible. In apreferred embodiment the capsule shells to be used may be those asdescribed in EP-A-0 891 180.

Surprisingly, it has been found that caplets coated with the coatingcomposition according to the present invention, show a superior adhesionto the capsule shell parts they have been filled in.

Especially, experimental results show that capsules filled with capletscoated with the coating composition according to the present invention,are tamper-proof in a way that the caplets show a superior adhesion tocapsule shell parts and a better adhesive strength than capsules of theprior art such as described in EP-A-0 891 180. This is also demonstratedbelow in the experimental part of the present specification.

If it was tried to remove capsule shell parts from capsules prepared byusing caplets coated according to the present invention, it was foundthat a very high percentage of shell parts will break and pulling apartcapsule shells without deteriorating the capsule shells is not possible.

Thus, in a further aspect the present invention provides a use of acoating composition comprising a film forming agent in an amount of from0 to about 85% by weight, an adhesion enhancing agent in an amount offrom about 10 to about 90% by weight, and a glidant in an amount of fromabout 5 to about 50% by weight, based on the weight of the coatingcomposition, for applying to a solid dosage form so as to improveadhesion of said solid dosage forms to capsule shells.

Furthermore, it has been found that feeding of caplets on a vibratoryfeed to be used in a capsule manufacturing process (typically the capletfeeding speed on a vibratory plate is in a range of from 1 to 7 cm/sec)is highly improved by using caplets coated with the coating compositionclaimed according to the present invention.

In a preferred embodiment of the process of preparing capsules by usingcaplets, in a further step caplets coated with the coating compositionclaimed according to the present invention are filled into capsule shellparts and then the combined capsule shell parts are treated by coldshrinking so as to obtain capsules.

As a preferred procedure the capsule manufacturing process described inEP-A-0 891 190 could be used.

To further illustrate the present invention, the following illustrativeexamples are presented, without limitation:

EXAMPLE 1

In a first example different coating compositions having a compositionas shown in Table 1 below, were coated on Capsugel 707 Placebo capletcores so as to obtain coated caplets. These coated caplets weresubjected to a feeding on a vibratory feed (caplet feeding speed onvibratory plate: 1 to 7 cm/sec). The behaviour of these coated capletswas visually tested, and the results obtained were the following: TABLE1 Mixture (ratio, parts by weight) vibratory feed HPMC/PVP 50/50 goodHPMC/HPC 40/60 good HPC/PEG 80/20 medium HPMC/HPC/PEG 20/60/20 mediumHPMC/HPC/PEG 30/50/20 medium HPMC/HPC/PEG 40/40/20 very goodAbbreviations used:HPMC = hydroxypropyl methylcellulosePVP = polyvinyl pyrrolidoneHPC = hydroxypropylcellulosePEG = polyethylene glycol 6000

EXAMPLE 2

Adhesion Results After Stability Storage

In this example samples of Press-fit gelcaps made with a standard HPMCcoating (sample 1) and made with a coating composition according to thepresent invention (sample 2) were manufactured according to a standardprocess. Sample 1 Cores Capsugel 707 Placebo * Shells Body White opaqueShells Cap Green opaque 3 months Defects Gap Appearance Quantity 40°C./75% RH 0 0 OK 150* coated with HPMC

Sample 2 Cores Capsugel 708 Placebo ** Shells Body White opaque ShellsCap Green opaque 3 months Defects Gap Appearance Quantity 40° C./75% RH0 0 OK 150** coated with a mix of HPMC/HPC/PEG (40/40/20)

Thereafter these samples were stored for 3 months under room conditionsand at 40° C. 75% RH, and adhesion and disintegration were measured.

Conclusions:

adhesion is stable at room conditions for both samples

at 40° C./75% RH the adhesion drops for the samples made with HPMCwhilst it remains stable for the sample made with the new coatingmixture.

Disintegration is equivalent for all samples and conforms tospecifications.

1. Adhesion Results: Nb of Pullapart (N) Std broken Sample 1 T = 24 h RC22.5 2.5 0% T = 6 days RC 22.7 4.1 0% T = 6 RC 21.1 2.9 0% weeks t = 2months RC 21.4 3.3 0% t = 3 RC 22.6 4.2 0% months t = 3 40° C./75% 8.43.0 0% months RH Sample 2 T = 24 h RC 29.13 5.0  80% T = 6 days RC 30.14.2 100% T = 6 RC 33.2 4.8  90% weeks t = 2 months RC 32.0 5.2  74% t =3 RC 28.5 3.1 100% months t =3 40° C./75% 27.2 3.7 100% months RH

2. Disintegration Results: Disintegration time STD Sample 1 T = 0 RC 4min 38 s 37 s T = 3 months 40° C./75% RH 5 min 06 s 19 s Sample 2 T = 0RC 3 min 41 s 29 s T = 3 months 40° C./75% RH 3 min 49 s 40 s

1. A coating composition comprising a film forming agent in an amount offrom 0 to about 85% by weight, an adhesion enhancing agent in an amountof from about 10 to about 90% by weight, and a glidant in an amount offrom about 5 to about 50% by weight, based on the weight of the coatingcomposition.
 2. The coating composition according to claim 1, whichcomprises a film forming agent in an amount of from about 0 to about 40%by weight, an adhesion enhancing agent in an amount of from about 35 toabout 80% by weight, and a glidant in an amount of from about 5 to about25% by weight based on the weight of the coating composition.
 3. Thecoating composition according to claims 1, wherein said film formingagent is hydroxypropyl methylcellulose.
 4. The coating compositionaccording to claims 1, wherein said adhesion enhancing agent ishydroxypropylcellulose.
 5. The coating composition according to claims1, wherein said glidant is polyethylene glycol.
 6. A solid dosage formcoated with a coating composition comprising a film forming agent in anamount of from 0 to about 85% by weight, an adhesion enhancing agent inan amount of from about 10 to about 90% by weight, and a glidant in anamount of from about 5 to about 50% by weight, based on the weight ofthe coating composition.
 7. The solid dosage form according to claim 6,wherein said solid dosage form is a caplet.
 8. A method of preparing acoating composition comprising ringing into association a film formingagent in an amount of from 0 to about 85% by weight, an adhesionenhancing agent in an amount of from about 10 to about 90 % by weight,and a glidant in an amount of from about 5 to about 50% by weight, basedon the weight of the coating composition.
 9. A method of preparing asolid dosage form which comprises coating a solid dosage form core witha coating composition comprising a film forming agent in an amount offrom 0 to about 85% by weight, an adhesion enhancing agent in an amountof from about 10 to about 90% by weight, and a glidant in an amount offrom about 5 to about 50% by weight, based on the weight of the coatingcomposition.
 10. The method according to claim 9, which furthercomprises the steps of filling the caplets coated with the coatingcomposition claimed according to the present invention into capsuleshell parts and treating the combined capsule shell parts so as toobtain capsules.
 11. The coating composition according to claim 2,wherein said adhesion enhancing agent is hydroxypropyl methylcellulose.12. The coating composition according to claim 2 wherein said adhesionenhancing agent is hydroxypropylcellulose.
 13. The coating compositionaccording to claim 3 wherein said adhesion enhancing agent ishydroxypropylcellulose.
 14. The coating composition according to claim 2wherein said glidant is polyethylene glycol.
 15. The coating compositionaccording to claim 3, wherein said glidant is polyethylene glycol. 16.The coating composition according to claim 4, wherein said glidant ispolyethylene glycol.